BACKGROUND AND PURPOSEBones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease. EXPERIMENTAL APPROACHRats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg -1 propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL-1b, TNF-a and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by ELISA, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-k B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro. RESULTSPropranolol at 0.1 and 5 mg·kg -1 reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only 0.1 mg·kg -1 reduced IL-1b, TNF-a and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and MMP-9. CONCLUSIONS AND IMPLICATIONSLow doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters. AbbreviationsAP, arterial pressure; BD, bone density; CTX, cross-linked carboxyterminal telopeptides of type I collagen; DMEM, Dulbecco's modified Eagle medium; DTT, dithiothreitol; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ICAM-1, intercellular adhesion molecule 1; LVEDP, left ventricular end-diastolic pressure; LVSP, left ventricular systolic pressure; NFAT, nuclear factor of activated T cells; OPG, osteoprotegerin; OVX, ovariectomized; RANKL, receptor activator of NF-k B ligand; SaM-1, human periosteum-derived osteoblastic cells; SaOS-2, human osteosarcoma-derived cells; SHR, spontaneous hypertensive rats; TBST, Tris-buffered saline-Tween; TRAP, tartrate-resistant acid phosphatase BJP British Journal of Pharmacology

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BackgroundChagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain.MethodsWe used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 102), medium (3 × 103), and high (3 × 104) parasite loads were generated by infecting C57BL/6 mice with “Y”-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey’s multiple comparison post-test, Kruskal–Wallis test with Dunn’s multiple comparison, χ2 test and Spearman correlation.ResultsHigh parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines.ConclusionsThese experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

Background COVID-19 is a highly transmissible illness caused by SARS-CoV-2. The disease has affected more than 200 countries, and the measures that have been implemented to combat its spread, as there is still no vaccine or definitive medication, have been based on supportive interventions and drug repositioning. Brazil, the largest country in South America, has had more than 140,000 recorded deaths and is one of the most affected countries. Despite the extensive quantity of scientifically recognized information, there are still conflicting discussions on how best to face the disease and the virus, especially with regard to social distancing, preventive methods, and the use of medications. Objective The main purpose of this study is to evaluate the Brazilian population’s basic knowledge about COVID-19 to demonstrate how Brazilians are managing to identify scientifically proven information. Methods A cross-sectional study design was used. An original online questionnaire survey was administered from June 16 to August 21, 2020, across all five different geopolitical regions of the country (ie, the North, Northeast, Center-West, Southeast, and South). The questionnaire was comprised of questions about basic aspects of COVID-19, such as the related symptoms, conduct that should be followed when suspected of infection, risk groups, prevention, transmission, and social distancing. The wrong questionnaire response alternatives were taken from the fake news combat website of the Brazilian Ministry of Health. Participants (aged ≥18 years) were recruited through social networking platforms, including Facebook, WhatsApp, and Twitter. The mean distributions, frequencies, and similarities or dissimilarities between the responses for the different variables of the study were evaluated. The significance level for all statistical tests was less than .05. Results A total of 4180 valid responses representative of all the states and regions of Brazil were recorded. Most respondents had good knowledge about COVID-19, getting an average of 86.59% of the total score with regard to the basic aspects of the disease. The region, education level, age, sex, and social condition had a significant association (P<.001) with knowledge about the disease, which meant that women, the young, those with higher education levels, nonrecipients of social assistance, and more economically and socially developed regions had more correct answers. Conclusions Overall, Brazilians with social media access have a good level of basic knowledge about COVID-19 but with differences depending on the analyzed subgroup. Due to the limitation of the platform used in carrying out the study, care should be taken when generalizing the study findings to populations with less education or who are not used to accessing social networking platforms.

Strategies for obtaining reliable results are increasingly implemented in order to reduce errors in the analysis of human and veterinary samples; however, further data are required for murine samples. Here, we determined an average factor from the murine body surface area for the calculation of biochemical renal parameters, assessed the effects of storage and freeze-thawing of C57BL/6 mouse samples on plasmatic and urinary urea, and evaluated the effects of using two different urea-measurement techniques. After obtaining 24 h urine samples, blood was collected, and body weight and length were established. The samples were evaluated after collection or stored at −20°C and −70°C. At different time points (0, 4, and 90 days), these samples were thawed, the creatinine and/or urea concentrations were analyzed, and samples were restored at these temperatures for further measurements. We show that creatinine clearance measurements should be adjusted according to the body surface area, which was calculated based on the weight and length of the animal. Repeated freeze-thawing cycles negatively affected the urea concentration; the urea concentration was more reproducible when using the modified Berthelot reaction rather than the ultraviolet method. Our findings will facilitate standardization and optimization of methodology as well as understanding of renal and other biochemical data obtained from mice.